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- miR-135b Aggravates Fusobacterium nucleatum-Induced Cisplatin Resistance in Colorectal Cancer by Targeting KLF13
- Wei Zeng , Jia Pan , Guannan Ye
- J. Microbiol. 2024;62(2):63-73. Published online February 24, 2024
- DOI: https://doi.org/10.1007/s12275-023-00100-1
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- 6 Web of Science
- 5 Crossref
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Abstract
- Cisplatin resistance is the main cause of colorectal cancer (CRC) treatment failure, and the cause has been reported to be related to Fusobacterium nucleatum (Fn) infection. In this study, we explored the role of Fn in regulating cisplatin resistance of CRC cells and its underlying mechanism involved. The mRNA and protein expressions were examined by qRT-PCR and western blot. Cell proliferation and cell apoptosis were assessed using CCK8 and flow cytometry assays, respectively. Dual-luciferase reporter gene assay was adopted to analyze the molecular interactions. Herein, our results revealed that Fn abundance and miR-135b expression were markedly elevated in CRC tissues, with a favorable association between the two. Moreover, Fn infection could increase miR-135b expression via a concentration-dependent manner, and it also enhanced cell proliferation but reduced apoptosis and cisplatin sensitivity by upregulating miR-135b. Moreover, KLF13 was proved as a downstream target of miR-135b, of which overexpression greatly diminished the promoting effect of miR-135b or Fn-mediated cisplatin resistance in CRC cells. In addition, it was observed that upstream 2.5 kb fragment of miR-135b promoter could be interacted by β-catenin/TCF4 complex, which was proved as an effector signaling of Fn. LF3, a blocker of β-catenin/TCF4 complex, was confirmed to diminish the promoting role of Fn on miR-135b expression. Thus, it could be concluded that Fn activated miR-135b expression through TCF4/β-catenin complex, thereby inhibiting KLF13 expression and promoting cisplatin resistance in CRC.
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Citations
Citations to this article as recorded by
- miR-135b: A Key Role in Cancer Biology and Therapeutic Targets
Yingchun Shao, Shuangshuang Zhang, Yuxin Pan, Zhan Peng, Yinying Dong
Non-coding RNA Research.2025;[Epub] CrossRef - Emerging roles of intratumor microbiota in cancer: tumorigenesis and management strategies
Zhuangzhuang Shi, Zhaoming Li, Mingzhi Zhang
Journal of Translational Medicine.2024;[Epub] CrossRef - Fusobacterium nucleatum: a novel regulator of antitumor immune checkpoint blockade therapy in colorectal cancer
Mengjie Luo
American Journal of Cancer Research.2024; 14(8): 3962. CrossRef - Antioxidant Role of Probiotics in Inflammation-Induced Colorectal Cancer
Sevag Hamamah, Andrei Lobiuc, Mihai Covasa
International Journal of Molecular Sciences.2024; 25(16): 9026. CrossRef - Identification of Penexanthone A as a Novel Chemosensitizer to Induce Ferroptosis by Targeting Nrf2 in Human Colorectal Cancer Cells
Genshi Zhao, Yanying Liu, Xia Wei, Chunxia Yang, Junfei Lu, Shihuan Yan, Xiaolin Ma, Xue Cheng, Zhengliang You, Yue Ding, Hongwei Guo, Zhiheng Su, Shangping Xing, Dan Zhu
Marine Drugs.2024; 22(8): 357. CrossRef
- miR-135b: A Key Role in Cancer Biology and Therapeutic Targets
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